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Protein

Protein kinase C zeta type

Gene

Prkcz

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro (By similarity).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei281ATPPROSITE-ProRule annotation1
Active sitei376Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri130 – 180Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi258 – 266ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • potassium channel regulator activity Source: Ensembl
  • protein kinase activity Source: MGI
  • protein kinase C activity Source: UniProtKB-EC
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Inflammatory response

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiR-MMU-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-MMU-5218921. VEGFR2 mediated cell proliferation.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C zeta type (EC:2.7.11.13)
Alternative name(s):
nPKC-zeta
Gene namesi
Name:Prkcz
Synonyms:Pkcz
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:97602. Prkcz.

Subcellular locationi

  • Cytoplasm By similarity
  • Endosome By similarity
  • Cell junction By similarity

  • Note: In the retina, localizes in the terminals of the rod bipolar cells. Associated with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. Colocalizes with VAMP2 and WDFY2 in intracellular vesicles.By similarity1 Publication

GO - Cellular componenti

  • apical cortex Source: MGI
  • apical plasma membrane Source: MGI
  • axon hillock Source: MGI
  • bicellular tight junction Source: MGI
  • cell-cell junction Source: UniProtKB
  • cell cortex Source: MGI
  • cell leading edge Source: Ensembl
  • cytoplasm Source: MGI
  • cytosol Source: Ensembl
  • endosome Source: UniProtKB-SubCell
  • extracellular exosome Source: MGI
  • filamentous actin Source: Ensembl
  • membrane raft Source: Ensembl
  • microtubule organizing center Source: MGI
  • myelin sheath abaxonal region Source: BHF-UCL
  • nuclear envelope Source: MGI
  • nuclear matrix Source: MGI
  • nucleus Source: MGI
  • perinuclear region of cytoplasm Source: Ensembl
  • plasma membrane Source: MGI
  • protein complex Source: MGI
  • vesicle Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Endosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557021 – 592Protein kinase C zeta typeAdd BLAST592

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei410Phosphothreonine; by PDPK1 and PI3KBy similarity1
Modified residuei560PhosphothreonineCombined sources1
Modified residuei591PhosphoserineBy similarity1

Post-translational modificationi

CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ02956.
PaxDbiQ02956.
PRIDEiQ02956.

PTM databases

iPTMnetiQ02956.
PhosphoSitePlusiQ02956.

Expressioni

Gene expression databases

BgeeiENSMUSG00000029053.
CleanExiMM_PRKCZ.
ExpressionAtlasiQ02956. baseline and differential.
GenevisibleiQ02956. MM.

Interactioni

Subunit structurei

Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 (By similarity). Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Interacts with PDPK1 (via N-terminal region) (By similarity). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529). Interacts with VAMP2 (PubMed:17313651). Forms a complex with WDFY2 and VAMP2 (PubMed:17313651).By similarity2 Publications

Protein-protein interaction databases

BioGridi202203. 26 interactors.
IntActiQ02956. 17 interactors.
MINTiMINT-98101.
STRINGi10090.ENSMUSP00000030922.

Structurei

3D structure databases

ProteinModelPortaliQ02956.
SMRiQ02956.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 98PB1PROSITE-ProRule annotationAdd BLAST84
Domaini252 – 518Protein kinasePROSITE-ProRule annotationAdd BLAST267
Domaini519 – 590AGC-kinase C-terminalAdd BLAST72

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni79 – 145Interaction with SQSTM1By similarityAdd BLAST67

Domaini

The C1 domain does not bind the diacylglycerol (DAG).
The PB1 domain mediate mutually exclusive interactions with SQSTM1 and PARD6B.By similarity

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 PB1 domain.PROSITE-ProRule annotation
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri130 – 180Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0695. Eukaryota.
ENOG410ZMG2. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ02956.
KOiK18952.
OMAiRCHVLVP.
OrthoDBiEOG091G03Q9.
TreeFamiTF102004.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR002219. PE/DAG-bd.
IPR012233. PKC.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000554. PKC_zeta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q02956-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPSRTDPKMD RSGGRVRLKA HYGGDILITS VDAMTTFKDL CEEVRDMCGL
60 70 80 90 100
HQQHPLTLKW VDSEGDPCTV SSQMELEEAF RLVCQGRDEV LIIHVFPSIP
110 120 130 140 150
EQPGMPCPGE DKSIYRRGAR RWRKLYRANG HLFQAKRFNR GAYCGQCSER
160 170 180 190 200
IWGLSRQGYR CINCKLLVHK RCHVLVPLTC RRHMDSVMPS QEPPVDDKND
210 220 230 240 250
GVDLPSEETD GIAYISSSRK HDNIKDDSED LKPVIDGVDG IKISQGLGLQ
260 270 280 290 300
DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE
310 320 330 340 350
KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE
360 370 380 390 400
EHARFYAAEI CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE
410 420 430 440 450
GLGPGDTTST FCGTPNYIAP EILRGEEYGF SVDWWALGVL MFEMMAGRSP
460 470 480 490 500
FDIITDNPDM NTEDYLFQVI LEKPIRIPRF LSVKASHVLK GFLNKDPKER
510 520 530 540 550
LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ TLPPFQPQIT DDYGLDNFDT
560 570 580 590
QFTSEPVQLT PDDEDVIKRI DQSEFEGFEY INPLLLSAEE SV
Length:592
Mass (Da):67,682
Last modified:July 27, 2011 - v2
Checksum:i690AD891C25BC311
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti197D → G in AAA39983 (PubMed:1487145).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94632 mRNA. Translation: AAA39983.1.
AL670413, AL670227 Genomic DNA. Translation: CAM20048.1.
AL670227, AL670413 Genomic DNA. Translation: CAM20648.1.
CH466594 Genomic DNA. Translation: EDL15000.1.
CCDSiCCDS19026.1.
PIRiJC1480.
RefSeqiNP_032886.2. NM_008860.3.
UniGeneiMm.28561.

Genome annotation databases

EnsembliENSMUST00000030922; ENSMUSP00000030922; ENSMUSG00000029053.
GeneIDi18762.
KEGGimmu:18762.
UCSCiuc008wdc.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M94632 mRNA. Translation: AAA39983.1.
AL670413, AL670227 Genomic DNA. Translation: CAM20048.1.
AL670227, AL670413 Genomic DNA. Translation: CAM20648.1.
CH466594 Genomic DNA. Translation: EDL15000.1.
CCDSiCCDS19026.1.
PIRiJC1480.
RefSeqiNP_032886.2. NM_008860.3.
UniGeneiMm.28561.

3D structure databases

ProteinModelPortaliQ02956.
SMRiQ02956.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202203. 26 interactors.
IntActiQ02956. 17 interactors.
MINTiMINT-98101.
STRINGi10090.ENSMUSP00000030922.

PTM databases

iPTMnetiQ02956.
PhosphoSitePlusiQ02956.

Proteomic databases

MaxQBiQ02956.
PaxDbiQ02956.
PRIDEiQ02956.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030922; ENSMUSP00000030922; ENSMUSG00000029053.
GeneIDi18762.
KEGGimmu:18762.
UCSCiuc008wdc.2. mouse.

Organism-specific databases

CTDi5590.
MGIiMGI:97602. Prkcz.

Phylogenomic databases

eggNOGiKOG0695. Eukaryota.
ENOG410ZMG2. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000233033.
HOVERGENiHBG108317.
InParanoidiQ02956.
KOiK18952.
OMAiRCHVLVP.
OrthoDBiEOG091G03Q9.
TreeFamiTF102004.

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiR-MMU-2173791. TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition).
R-MMU-5218921. VEGFR2 mediated cell proliferation.

Miscellaneous databases

PROiQ02956.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000029053.
CleanExiMM_PRKCZ.
ExpressionAtlasiQ02956. baseline and differential.
GenevisibleiQ02956. MM.

Family and domain databases

CDDicd00029. C1. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR000270. PB1_dom.
IPR002219. PE/DAG-bd.
IPR012233. PKC.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000554. PKC_zeta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiKPCZ_MOUSE
AccessioniPrimary (citable) accession number: Q02956
Secondary accession number(s): A2AD76
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 177 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.